In 2013 we reported (Bodogai et al. Cancer Research, 2013) new markers that can be used for characterization of tBregs, such as besides CD19+ CCR6+ CD25High CD81High B7-H1 High CD86 High CD62Low IgM Int/Low, they can also be defined by low expression of CD20 and 4-1BBL. Importantly, clinical relevance of tBregs expressing low levels of 4-1BBL on tBregs is to prevent activation of effector antitumor CD8 T cells. Utilizing CD20-low as a marker of tBregs, we also found that some human B-CLL can be derived from tBregs. Thus, these results further reinforce our original hypothesis that tBregs also exist in humans with cancer. Our modeling studies indicate that the CD20-Low status of tBregs protects them from depletion with rituximab/ant-CD20 antibody. In mice with breast cancer, anti-CD20 Ab treatment is instead harmful and augments cancer escape and metastasis via enriching tBregs. These results also provide a mechanistic explanation of a recent failure of rituximab treatment in humans with solid tumors.Our results (Olkhanud et al, Cancer Research, 2009; 2011; Bodogai et al. Cancer Research, 2013) indicate the importance of tBregs and concurrently Tregs in regulation of anticancer responses to facilitate cancer escape and metastasis. In contrast, others reported that cancer expands MDSC to metastasize. Here we report that MDSCs fail to support metastasis if B cells are deficient, as their regulatory activity is impaired in the absence of tBregs. We found that cancer targets B cells, such as tumor-evoked regulatory B cells (tBregs) to render MDSCs regulatory. Utilizing TGFb-Tgfr1/Tgfr2 axis tBregs increase suppressive and thereby pro-metastatic activity of tumor-expanded PMN- and Mo-MDSCs. Thus, the cancer-induced expansion of MDSCs per se is not criteria of their regulatory state; the regulatory activity of MDSCs requires an additional activation pathway, tBregs/B cells. We recently reported (Wejksza et al., J. Immunology, 2013) that cancer cells target the proliferator-activated receptor alpha (PPARa) signaling to induce the generation of tBregs via metabolites of the 5-lipoxygenase (5-LO) pathway. Inactivation of LTB4 signaling or genetic deficiency of PPARa in B cells blocks the generation of tBregs and thereby abrogates lung metastasis in mice with established breast cancer. Thus, in addition to eliciting fatty acid oxidation and metabolic signals, PPARa initiates programs required for differentiation of tBregs. We propose that PPARa in B cells or/and tumor 5-LO pathways represents new targets for pharmacological control of tBreg mediated cancer escape. Here, we report that cancer uses exosomes to deliver 5-LO metabolites to B cells. Cancer exosomes converted tBregs as efficiently as cancer conditioned media. This is very interesting result with significant clinical relevance. A rising interest in our study resulted in publication of two invited book chapters (Lee-Chang, C., et al., he Tumor ImmunoEnvironment. Springer, 2013; and Biragyn et al. Regulatory B cells, Humana press, 2014).